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Transcript
• Originally taught at Bryn Mawr (1890-1904)
• Moved to Columbia University in 1904;
founded the famous fruit fly lab (the “Fly
Room”, 613, Schermerhorn Hall, measuring
only 16 x 23 feet and containing eight desks,
but host to many famous researchers
including Nobel laureates Hermann J. Müller
(1946), George W. Beadle (1958), Joshua
Lederberg (1958) , and Edward B. Lewis
(1995); Theodosius Dobzhansky, who forged
the synthesis between genetics and evolution, also worked there.
• Spent many summers at the MBL in Woods Hole, MA
• Moved to California to head the Division of Biology at the California Institute of
Technology in 1928. Stayed until he retired in 1942. Three more Nobel laureates
came out of that lab: George Beadle and Edward L. Tatum (1958), and Linus
Pauling (1954).
After some two years of breeding fruit-flies,
Morgan found a mutation that bred true,
namely “white-eye”. However, the mutation
was much more common in males than in
females. Breeding a red-eyed female to a
white-eyed male appears to follow simple
Mendelian dominance: all offspring are redeyed. But the reciprocal cross of a red-eyed
male to a white-eyed female produces only
white-eyed males.
Xw- implies a
recessive
gene on the X
chromosome.
There is no
equivalent on
the Y
FYI: 223=83,88,608 unique sperm or eggs. Times 2 = 16,777,216 unique babies from one
man and one woman.
When homologous chromosomes pair up
in metaphase I they can exchange
material. This leads to a far greater variety
of gametes than meiosis alone.
The probability of a crossover is directly proportional to
the distance between two genes. The standard unit of
genetic distance is expressed in morgans.
A morgan is distance on the genetic map: it is defined as
the distance between two loci such that on average one
crossing over will occur per meiosis; for working purposes,
the centimorgan (0.01 M) is used.
For those mathematically inclined,
1
𝑑 = 50 ln
1 − 2Pr(𝑟𝑒𝑐𝑜𝑚𝑏𝑖𝑛𝑎𝑡𝑖𝑜𝑛)
Where d is in centimorgans.
(on average, a centimorgan is equivalent to 15kb DNA)
One evening in 1913 one of Morgan’s students, Alfred
Sturtevant took home some of Morgan’s breeding records.
Reasoning that the closer genes are on the chromosome the
less likely they are to cross over with the homologous
chromosome, he worked all night and the next morning
presented Morgan with a linear arrangement of the genes on
the X chromosome.
Sturtevant was 19 at the time.
In 1928 he moved with Morgan to CIT. He became the leader
of a new genetics research group at Caltech, whose members
included George W. Beadle (with whom he wrote a genetics
text) and Theodosius Dobzhansky. He was elected a Fellow of
the American Academy of Arts and Sciences in 1949. In 1967
he received the National Medal of Science for his longtime
work on the genetics of Drosophila and other organisms.
He died in 1970
Following upon Müller’s work with
irradiation, Beadle and Tatum used
irradiation to produce mutations in
Neurospora.
They switched from Drosophila because
the vegetative form of Neurospora is
haploid, so there are no dominance and
recessive effects. Every gene is
expressed individually.
They made many cultures on
minimal medium from irradiated
samples. Most grew just fine. The
299th one, however, would not
grow unless supplemented.
Many such experiments led to
(among others) three mutants
which needed certain amino acids
in order to grow.
The results of their experiments
confirmed the idea that each
mutation of a single gene affects a
single enzyme protein.
In typical conjugation, a
plasmid (F factor) is
transferred from an F+
(donor) to an F- (recipient)
making both F+
In a few cases part (or even all) of the donor’s
chromosomal DNA is transferred. Since it is
transferred in a linear sequence and interrupted
at random times it is possible to infer from the
resultant changes in the recipient the sequence
of genes on the chromosome as well as their
discrete nature.
The lac operon is actually a “cassette” consisting of
both regulatory and structural genes in e. coli, all
targeted toward the utilization of lactose as an energy
source.
The structural genes are all in a linear sequence on the
DNA, allowing a single transcription event to produce
all three enzymes.
So as to prevent wasting resources by producing the enzymes in the absence of
lactose or presence of glucose, two other proteins are involved. Both repress
expression of the structural genes by binding to the promoter region. One
repressor protein is activated by glucose, and the other (lacl) is inactivated in
the presence of lactose. This second protein is coded for just upstream of the
operon itself.
Barbara McClintock was born in 1902. She received her BSc (1923),
and PhD (1927)in botany from Cornell’s College of Agriculture. At
Cornell she developed staining techniques to visualize maize
chromosomes. By 1929, she had refined these techniques
sufficiently to discriminate between each of the 10 maize
chromosomes, allowing researchers to link genetic data to the
behavior of chromosomes. She also helped identify all of the maize
linkage groups.
By 1932 McClintock had published nine articles on maize
chromosomes, including studies of the centromere and the
nucleolus, and a landmark 1931 PNAS article in which she and
graduate student Harriet Creighton demonstrated genetic crossingover at the chromosomal level and showed that genetic
recombination involved the physical exchange of chromosome
segments, a major contribution to the field of genetics.
“You just know sooner or later, it will come out in the wash,
but you may have to wait some time,” McClintock said after receiving the prize.
•
•
•
•
•
Elizabeth Helen Blackburn, AC, FRS,FAA, FRSN
Born 26 November 1948, Tasmania
Presently at the University of California, San Francisco (since 1990)
president-elect of the American Association for Cancer Research.
Also works in medical ethics
• Appointed a member of the President's Council on Bioethics in 2002.
• Terminated by White House directive on 27 February 2004 because she supported human
embryonic cell research, in opposition to the Bush Administration.
• "There is a growing sense that scientific research—which, after all, is defined by the quest for truth—is
being manipulated for political ends. There is evidence that such manipulation is being achieved
through the stacking of the membership of advisory bodies and through the delay and
misrepresentation of their reports.“ (Blackburn, N Eng. J Med 350:1379–1380 (1 April 2004))
• Serves on the Science Advisory Board of the Genetics Policy Institute.
Carolyn Widney "Carol" Greider
born April 15, 1961
Bloomberg Distinguished Professor, Daniel Nathans
Professor and Director of Molecular Biology and
Genetics at Johns Hopkins University.
Discovered the enzyme telomerase in 1984, when she was a graduate
student of Elizabeth Blackburn at the University of California, Berkeley.
Dyslexic. Says that her "compensatory skills also played a role in my success
as a scientist because one has to intuit many different things that are going
on at the same time and apply those to a particular problem"
DNA polymerase can only
work on dsDNA; RNA
polymerase can work on
ssDNA